Use of a Slow-Release Phenylalanine-Free Microtablet Protein Substitute in Children and Adolescents with...

Background/Objectives: In phenylketonuria (PKU), adherence to protein substitute (PS) is frequently suboptimal due to poor palatability, high volume, and sensory fatigue. A novel phenylalanine (Phe)-free L-amino acid microtablet PS has been developed to address these barriers. The microtablets incorporate a cellulose-based taste-masking coating and a sodium-alginate inner matrix intended to enable controlled amino acid release over approximately three hours. This study evaluated their short-term tolerability, acceptability, and adherence in children with PKU, with extended follow-up in a subgroup. Methods: A 7-day observational study was conducted in participants with PKU aged ≥3 years on a low-Phe diet in a single centre. The test product provided protein equivalent (PE) 54 g/100 g. Participants replaced at least one daily dose of their usual PS with the test product, providing 10 g or 20 g/day PE, with one child receiving 80 g/day. Daily gastrointestinal (GI) symptoms, PS intake, and adherence were recorded. Acceptability was assessed using structured ratings of palatability, ease of use, and overall preference. Longer-term tolerability and acceptability were then assessed in four adolescents who elected to continue the test product for an additional 28 days. Results: Ten participants completed the 7-day study. Adherence to the test product was high (80%), exceeding adherence to participants' usual PS (70%). At baseline, nine participants reported none/mild GI symptoms, most commonly flatulence. One participant reported moderate/severe symptoms including constipation, flatulence, diarrhoea, bloating, burping, and abdominal discomfort. By day 7, all participants reported no or mild symptoms, with complete resolution in the child with moderate/severe baseline symptoms. Acceptability ratings were comparable between the test product and usual PS, and nine children (90%) reported no difficulty taking the test product. During the 28-day extension, adherence remained high, GI tolerance was maintained, and improved preference was noted, particularly due to reduced aftertaste. Conclusions: This novel slow-release PS microtablet was well tolerated, acceptable, and associated with high adherence. Its taste-masked, low-volume format offered practical advantages that may support sustained dietary adherence. Longer-term controlled studies are necessary to confirm these findings.